phase ii study of ftd/tpi (lonsurf) in metastatic breast cancers with or without prior exposure to fluoropyrimidines (lonbreca)

Conditions: Breast Cancer

Summary: this is a single arm, open-label, lead in phase ib dose confirmation, followed by phase ii study with 2 parallel study cohorts.

phase ib patients will be treated with twice-daily dosing of ftd/tpi in a 3+3 dose escalation design phase ii oral ftd/tpi at rp2d will be administered until disease progression, intolerable toxicity or patient withdrawal. 2 parallel cohorts of patients will be enrolled : cohort a : patients with prior exposure to fluoropyrimidines cohort b : patients without prior exposure to fluoropyrimidines

Eligibility criteria:
inclusion criteria: * age ≥ 21 years. * histological or cytological diagnosis of breast carcinoma. * ecog 0-2. * her2 negative tumor (ihc 0 -1+ or ihc 2+ and confirmed on her2 fish to be negative based on histological report). * patients with her2 positive tumor may be enrolled if they have failed at least two lines of anti-her2 based therapies in the metastatic setting, or are intolerant to trastuzumab * any hormone receptor status. * any number of lines of prior palliative endocrine therapy for patients with hormone receptor positive cancer. * has measureable or evaluable disease based on recist 1.1 criteria * estimated life expectancy of at least 12 weeks. * has documented progressive disease from last line of therapy. * has recovered from acute toxicities from prior anti-cancer therapies * adequate organ function including the following: obone marrow: (i) absolute neutrophil (segmented and bands) count (anc) ≥1.5 x 109/l (ii) platelets ≥100 x 109/l (ii) hemoglobin ≥8 x 109/l ohepatic: (i)bilirubin ≤ 1.5 x upper limit of normal (uln), (ii)alt or ast ≤ 2.5x uln, (or ≤ 5 x with liver metastases) orenal: (i) creatinine ≤1.5x uln * signed informed consent from patient or legal representative. * able to comply with study-related procedures. * prior therapy (patients enrolled in phase ib may be enrolled if they fulfil prior therapy criteria for either cohort a or cohort b) * cohort a only: has received at least 2 lines of palliative systemic therapy, including prior fluropyrimidines (capecitabine, ts-1 or 5-fluorouracil) in the palliative setting, or in the adjuvant setting; patients who have only prior exposure to adjuvant fluoropyrimidines must have relapsed within 12 months of completing adjuvant fluoropyrimidines * cohort b only: any number of prior lines of palliative chemotherapy and has not received fluoropyrimidines (capecitabine, ts-1 or 5-fluorouracil) in the palliative setting or in the adjuvant setting; patients who have prior exposure to adjuvant fluoropyrimidines are eligible if they have relapsed 12 months from completion of adjuvant fluoropyrimidines. exclusion criteria: * treatment within the last 30 days with any investigational drug. * concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy. * major surgery within 28 days of study drug administration. * active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy. * pregnancy. * breast feeding. * serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator. * active bleeding disorder or bleeding site. * non-healing wound. * poorly controlled diabetes mellitus. * second primary malignancy that is clinically detectable at the time of consideration for study enrollment. * symptomatic brain metastasis. * history of significant neurological or mental disorder, including seizures or dementia. * unable to comply with study procedures phase ib lead-in can recruit patients who fulfil criteria for either cohort a or cohort b and all other inclusion/exclusion criteria

Keywords: ftd/tpi tas-102 trifluridine